PROJECT SUMMARY Accurate localization of the seizure onset area in patients with medically refractory focal epilepsies is crucial for successful neurosurgical treatment using interventions such as tissue resection, laser ablation and brain stimulation. However, current localization approaches have serious shortcomings because they are time- consuming, expensive, qualitative and do not necessarily lead to seizure control. To overcome this hurdle, we propose to validate a novel and powerful approach, termed brain interictal network mapping ? BINMAP ? by which a brief segment of the brain?s interictal (background) activity will be used to first establish a frequency band-specific functional connectivity map and then this map will be used to accurately delineate the seizure onset area in focal epilepsies. The objective here is to validate the BINMAP approach in patients with different types of focal epilepsies and rodent models of focal neocortical epilepsy. The central hypothesis is that BINMAP will delineate the seizure onset area more effectively and accurately than current approaches and reduce the cost and patient discomfort and improve the outcome of epilepsy surgery. The first aim of the project is to optimize and validate BINMAP in 120 patients with neocortical and mesial temporal lobe epilepsies. The method will be conducted on the interictal intracranial electroencephalogram (icEEG) and scalp EEG, sampled at multiple time points during continuous, up to 2-week long, inpatient monitoring procedures. The second aim will be to use two established rodent models of focal neocortical epilepsy, to understand the mechanisms underlying the development of both a biomarker for post-lesion epilepsy and the functional connectivity detected by BINMAP. To this end, discrete epileptogenic lesions will be created in the neocortex of rats, followed by BINMAP monitoring of the epileptogenic process. The research is innovative for two reasons. First, it uses a brief segment of interictal icEEG, versus seizure recordings obtained over several days of continuous long-term monitoring, to delineate the seizure onset area in patients with epilepsy. Second, it aims to understand the mechanism underlying the development of functional connectivity in focal neocortical epilepsies during epileptogenesis. The expected outcome of this study will both help elucidate the network changes which accompany epileptogenesis and transform the way clinicians locate the seizure onset area by replacing expensive and time-consuming icEEG recordings with analysis of interictal icEEG. If successful, this project will have a high translational impact because it will dramatically reduce the cost and increase the accuracy of seizure onset area localization, thereby lowering health expenses and increasing the success of epilepsy surgery.